TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer

Ann Surg. 2002 Apr;235(4):493-8. doi: 10.1097/00000658-200204000-00006.


Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer.

Summary background data: Recent studies show that p53 may be a determinant of radiosensitivity being required for induction of apoptosis in case of radiation-induced DNA damage.

Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively.

Results: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51.

Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma / diagnostic imaging*
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Female
  • Gene Expression / genetics
  • Gene Expression / immunology
  • Genes, p53 / genetics*
  • Genes, p53 / immunology*
  • Humans
  • Immunohistochemistry*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Mutation / immunology
  • Predictive Value of Tests
  • Preoperative Care
  • Radiography
  • Rectal Neoplasms / immunology*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome